Detectable Serum HCV-RNA Research Articles

Ledipasvir/Sofosbuvir Is Effective as Sole Treatment of Porphyria Cutanea Tarda with Chronic Hepatitis C.

Chronic hepatitis C [CHC] is a risk factor for porphyria cutanea tarda [PCT]. To assess whether ledipasvir/sofosbuvir is effective for treating both PCT and CHC, we treated patients with CHC + PCT solely with ledipasvir/sofosbuvir and followed them for at least 1year to assess cure of CHC and remission of PCT. Between September 2017 and May 2020, 15 of 23 screened PCT + CHC patients were eligible and enrolled. All were treated with ledipasvir/sofosbuvir at recommended doses and durations, according to their stage of liver disease. We measured plasma and urinary porphyrins at baseline and monthly for the first 12months and at 16, 20, and 24 mos. We measured serum HCV RNA at baseline, 8-12, and 20-24 mos. Cure of HCV was defined as no detectable serum HCV RNA ≥ 12weeks after the end of treatment (EOT). Remission of PCT was defined clinically as no new blisters or bullae and biochemically as urinary uro- plus hepta-carboxyl porphyrins ≤ 100 mcg/g creatinine. All 15 patients, 13 of whom were men, were infected with HCV genotype 1. 2/15 withdrew or were lost to follow-up. Of the remaining 13, 12 achieved cure of CHC; 1 had complete virological response, followed by relapse of HCV after ledipasvir/sofosbuvir but was subsequently cured by treatment with sofosbuvir/velpatasvir. Of the 12 cured of CHC, all achieved sustained clinical remission of PCT. Ledipasvir/sofosbuvir [and likely other direct-acting antivirals] is an effective treatment for HCV in the presence of PCT and leads to clinical remission of PCT without additional phlebotomy or low-dose hydroxychloroquine treatment. ClinicalTrials.gov NCT03118674.

Global prevalence of occult hepatitis C virus: A systematic review and meta-analysis.

BACKGROUNDOccult hepatitis C infection (OCI) is characterized by the presence of hepatitis C virus (HCV) RNA in the liver, peripheral blood mononuclear cells (PBMC) and/or ultracentrifuged serum in the absence of detectable HCV-RNA in serum. OCI has been described in several categories of populations including hemodialysis patients, patients with a sustained virological response, immunocompromised individuals, patients with abnormal hepatic function, and apparently healthy subjects.AIMTo highlight the global prevalence of OCI.METHODSWe performed a systematic and comprehensive literature search in the following 4 electronic databases PubMed, EMBASE, Global Index Medicus, and Web of Science up to 6th May 2021 to retrieve relevant studies published in the field. Included studies were unrestricted population categories with known RNA status in serum, PBMC, liver tissue and/or ultracentrifuged serum. Data were extracted independently by each author and the Hoy et al tool was used to assess the quality of the included studies. We used the random-effect meta-analysis model to estimate the proportions of OCI and their 95% confidence intervals (95%CI). The Cochran's Q-test and the I2 test statistics were used to assess heterogeneity between studies. Funnel plot and Egger test were used to examine publication bias. R software version 4.1.0 was used for all analyses.RESULTSThe electronic search resulted in 3950 articles. We obtained 102 prevalence data from 85 included studies. The pooled prevalence of seronegative OCI was estimated to be 9.61% (95%CI: 6.84-12.73) with substantial heterogeneity [I² = 94.7% (95%CI: 93.8%-95.4%), P < 0.0001]. Seropositive OCI prevalence was estimated to be 13.39% (95%CI: 7.85-19.99) with substantial heterogeneity [I2 = 93.0% (90.8%-94.7%)]. Higher seronegative OCI prevalence was found in Southern Europe and Northern Africa, and in patients with abnormal liver function, hematological disorders, and kidney diseases. Higher seropositive OCI prevalence was found in Southern Europe, Northern America, and Northern Africa.CONCLUSIONIn conclusion, in the present study, it appears that the burden of OCI is high and variable across the different regions and population categories. Further studies on OCI are needed to assess the transmissibility, clinical significance, long-term outcome, and need for treatment.

2278 Rapidly Progressive Hepatitis C After Liver Transplantation Treated With Glecaprevir/Pibrentasvir

INTRODUCTION: Hepatitis C recurrence following liver transplantation occurs in all patients with chronic HCV infection who have detectable serum HCV RNA levels prior to transplant. Less than 10% of these patients develop an acute and severe phenotype called fibrosing cholestatic hepatitis, which often involves fibrosis, rapid graft loss and decreased survival. The introduction of direct-acting antiviral agents (DAAs) have changed the paradigm of treatment of these patients. CASE DESCRIPTION/METHODS: A 62-year-old woman with a medical history of hepatitis C infection, hepatocellular carcinoma status post orthotropic liver transplantation, diabetes mellitus and hypertension who was hospitalized for fatigue and elevated liver chemistries following her liver transplantation. Laboratory tests showed a white cell count 6.67 × 103/μL, creatinine 1.1 mg/dL, aspartate aminotransferase 592 U/L, alanine aminotransferase 504U/L, alkaline phosphatase 312 U/L, bilirubin 3.5 mg/dL, albumin 2.9 g/dL. Acute hepatitis work up showed a positive hepatitis C virus antibodies with genotype 1B, with a viral load of 80 million IU/mL HCV RNA. HBsAg, HBc IgG, HBc IgM, and hepatitis A virus IgM were negative. Evaluation for Epstein-Barr virus, cytomegalovirus and herpes simplex virus were negative. Ultrasound of the abdomen revealed that the liver is normal in size, echotexture and contours. No focal hepatic lesions. Normal hepatic blood flow. The patient underwent liver biopsy that showed lymphocytic portal inflammation with frequent lobular apoptosis consistent with active chronic hepatitis C (MHAI: 5-6/18). Mild portal fibrosis (ISHAK FIBROSIS STAGE: 1/6) and minimal evidence of acute t cell-mediated rejection (rejection activity index: 1/9). During the patient hospitalization her liver chemistries significantly worsened and peaked to aspartate aminotransferase 740 U/L, alanine aminotransferase 511U/L, alkaline phosphatase 312 U/L, bilirubin 3.5 mg/dL. We decided to start the patient on Glecaprevir/Pibrentasvir for acute and severe hepatitis. Fourteen days after starting Glecaprevir/Pibrentasvir, the patient viral load decreased to 782 IU/mL HCV RNA and normalized liver chemistries with AST19 and ALT 27. The patient denied any adverse events due to the treatment. DISCUSSION: To our knowledge, this is the first case report of treating early and aggressive form of HCV recurrence with Glecaprevir/Pibrentasvir. The dramatic improvement of the patient suggest that DAA might be safe and effective in this situation.

Incidence and risk factors of early HCC occurrence in HCV patients treated with direct acting antivirals: a prospective multicentre study

BackgroundAn unexpected increased HCC recurrence and occurrence rate among HCV patients treated with direct acting antivirals combination has been reported. Aim of the study was the evaluation of early HCC occurrence rate and its risk factors in a HCV infected population, treated with direct-acting-antivirals.MethodsAccording to the Italian ministerial guidelines for direct-acting-antivirals treatment, 1022 consecutive HCV patients treated with direct-acting-antivirals were enrolled. Patients either with active HCC at imaging or history of previous treated HCC, HBV or HIV co-infection, or liver transplant recipients were excluded. The SVR, defined as the persistent absence of detectable serum HCV-RNA 12 weeks after the end of treatment (SVR12), was assessed for all enrolled patients. Abdominal ultrasound was performed before starting antiviral therapy, and repeated every 6 months. HCC was diagnosed according to the international guidelines. Patients showing either nodular patterns suggestive of HCC or with uncertain dynamic vascular behaviour were excluded from a further follow-up.ResultsNine hundred and eighty-five patients completed the 48 weeks follow-up after the end of treatment. A Sofosbuvir-based regimen was administered in the 74.9% of patients, among whom, the 71.6% underwent a simultaneous Ribavirin administration. A sustained virological response at 12 weeks off treatment was documented in 966 patients (98.2%). During the post treatment follow-up HCC was detected in 35 patients, with a cumulative incidence rate of the 3.55%. At multivariate analysis, four variables resulted independently associated with HCC development, both in a cirrhosis based and a class B Child based model, respectively: cirrhosis/class B Child, therapeutic schedule including Sofosbuvir without Ribavirin, liver stiffness values, male gender and presence of diabetes. A multivariate analysis performed on Child A cirrhotic patients, showed that Sofosbuvir based therapeutic treatment without Ribavirin had a HCC occurrence 5.7 higher than Ribavirin-based schedules with or without Sofosbuvir (p < 0.0001, OR: 5.686, 95% CI 2.455–13.169).ConclusionsOur data suggest that early HCC occurrence appears more frequently related to Sofosbuvir-based therapy without Ribavirin which, indeed, seems to play a protective role on HCC onset. Therefore, a careful follow-up should be mandatory, especially in those regimens including Sofosbuvir without Ribavirin.

Predictors of hepatitis C virus recurrence after living donor liver transplantation: Mansoura experience

Background and study aimsHepatitis C virus (HCV)-related cirrhosis is the leading cause of liver transplantation (LT). All patients who undergo LT with detectable serum HCV-RNA experience graft reinfection, which is the most frequent cause of graft loss and death in these patients. We estimated the rate of HCV recurrence and evaluated the current therapeutic regimens. Patients and methodsThe records of consecutive 325 living donor LT (LDLT) surgeries performed between May 2004 and August 2014 were retrospectively analysed; 207 of them were followed-up throughout the study. Clinical, laboratory, radiological and histopathological examinations were performed thoroughly. Patients received treatment in the form of either pegylated interferon (PEG-IFN) or sofosbuvir, both in combination with ribavirin. ResultsIn total, 90.3% of recipients who were transplanted because of HCV-related end-stage liver disease experienced recurrence due to the virus. The donor age was older in the HCV recurrent group versus the non-recurrence group (28.7±7.1 versus 22.6±2.6years: p≤0.001), warm ischaemia time was prolonged (46.1±18.1 versus 28.6±4.1min: p≤0.001), median cold ischaemia time was 40.0 (10–175) versus 22.5 (15–38) min (p≤0.001) and basal PCR was 414000 (546-116000000) versus 10766 (1230-40000) (p≤0.001). Sustained virological response was achieved in 95.4% of patients treated with a combination of a fixed daily dose of 400mg sofosbuvir with ribavirin and in 65.1% of those who were treated with PEG-IFN with ribavirin. ConclusionsOlder donor age and prolonged warm ischaemia time are independent predictors of HCV recurrence after LDLT, and early treatment with the direct-acting sofosbuvir is helpful in resolving the problem of post-LT HCV recurrence.

Early Viral Response Predicts the Efficacy of Antiviral Triple Therapy with Simeprevir, Peg-Interferon and Ribavirin in Patients Infected with Hepatitis C Virus Genotype 1

Objectives: Triple therapy using peg-interferon, ribavirin and simeprevir (PEG-IFN/RBV/SMV) has reportedly resulted in high-sustained virological response (SVR) rates in patients with chronic hepatitis C (CHC), especially in naïve cases and relapsers to prior PEG-IFN/RBV therapy. Here, we retrospectively analyzed the antiviral response associated with a triple regimen, in the context of early reduction of viral load during treatment. Methods: Forty-six CHC patients with HCV genotype 1b were treated with PEG-IFN/RBV/SMV triple therapy: 20 were naïve cases, 12 were relapsers and 14 were non-responders to prior PEG-IFN/RBV therapy. We evaluated rapid virological response (RVR), complete early virological response (EVR), viral clearance at the end of the treatment (EOT) and at 12 weeks after the EOT (SVR12). In addition, we quantified the serum HCV-RNA on the 1st day and the 7th day after initiating treatment. Results: Multivariate analysis revealed that response to prior treatment was identified as an independent factor for achieving SVR12 after triple therapy (p = 0.0005). The achievement of serum HCV-RNA <2 log₁₀ IU/ml on day 7, RVR, EVR and EOT were associated with SVR12 (p = 0.0050, p = 0.0002, p = 0.0009 and p = 0.0002, respectively). Conclusions: Rapid decline of HCV is a predictive factor for the achievement of SVR12, even in antiviral triple therapy with PEG-IFN/RBV/SMV. An extended treatment period should be applied for patients who show detectable serum HCV-RNA at week 4.

Rate and predictors of serum HCV-RNA >6 million IU/mL in patients with chronic hepatitis C

BackgroundBaseline serum HCV-RNA predicts sustained virological response in chronic hepatitis C patients treated with antiviral therapy. A threshold at 6 million IU/mL has been proposed to best discriminate treatment outcomes on sofosbuvir-based regimens. In comparison with the general population, immunosuppressed individuals exhibit greater viral load values. ObjectivesTo estimate the rate and predictors of serum HCV-RNA above 6 millionIU/mL in chronic hepatitis C patients on care outside clinical trials. Study designSerum HCV-RNA values recorded from all chronic hepatitis C patients consecutively attended at our clinic during the last decade were analyzed. Testing had been performed using the COBAS TaqMan HCV test v2.0. ResultsA total of 816 individuals with detectable serum HCV-RNA were identified. The main characteristics of this population were as follows: mean age 48.6 years-old; 73.4% males; mean ALT 82.6IU/L; mean HCV-RNA 6.02logIU/mL; 80.6% HCV genotypes 1 or 4; 34.9% advanced liver fibrosis; 35.4% IL28B-CC alleles. HIV coinfection in 78.7%, of whom 91% were on antiretroviral therapy.Overall, 127 (15.6%) had serum HCV-RNA values >6 millionIU/mL. This high viremia was found in 18.2% of HIV-positive versus 5.7% of HIV-negative subjects (p<0.001). In multivariate analysis, serum HCV-RNA >6 millionIU/mL was only significantly associated with HIV coinfection (OR: 4.03; 95% CI: 1.98–8.19, p<0.01) and HCV genotypes 1 or 4 (OR: 1.88; 95% CI: 1.05–3.37, p=0.03). ConclusionsSerum HCV-RNA >6 millionIU/mL is roughly seen in 6% of chronic hepatitis C monoinfected patients, and increases up to 18% in HIV coinfection.

Hepatitis C (HCV) Treatment and SVR: The Gap Between Clinical Trials and the Real-World

Introduction: Telaprevir, a NS3A/4 protease inhibitor, in combination with peginterferon-ribavirin [PEG-IFN/RBV] has proven to be associated with significantly improved rates of SVR in patients with HCV genotype 1 infection who have not received any previous treatment (N Engl J Med 2011;364:2405-16). The purpose of this study was to compare our results in a single practice with the results of previously published controlled studies. Methods: A single center retrospective cohort study was conducted on patients with HCV genotype 1 infection who had previously not received treatment for the infection. Fifty-one patients received triple therapy with Telaprevir combined with PEG-IFN/RBV for 12 weeks, followed by PEG-IFN/RBV alone for 12 and 36 weeks in non-cirrhotic and cirrhotic patients, respectively. End of treatment (EOT) was defined as a total of 24 weeks of therapy for non-cirrhotic patients and 48 weeks of therapy for cirrhotic patients. HCV RNA levels were measured at treatment weeks 4, 8, 12, 36, 48 and at post-treatment weeks 4 and 12 using a sensitive TMA assay (lower limit of detection of 5 IU/L). Viral relapse was defined as re-appearance of detectable serum HCV RNA between EOT and post treatment. SVR was defined as undetectable HCV RNA at 12 weeks post treatment. The primary end point was the proportion of patients who had undetectable HCV RNA at 12 weeks post therapy. Results: Of the 51 patients treated, 10 patients had cirrhosis. The overall rate of SVR was 51% (26). Three out of the 10 cirrhotic patients achieved SVR (30%) and 23 out of 41 non-cirrhotic patients achieved SVR (56%). Of the 35 patients who completed therapy, 24 achieved SVR (69%), 4 relapsed (11%) and 7 did not follow up post therapy (20%). Therapy was terminated in 16 patients. Discontinuation was based on adverse events in 18% of patients overall, including severe anemia (4), rash (2), blurred vision (1), intolerance (1), and hallucinations (1). Two patients had virologic breakthrough (13%), 1 did not follow up (6%), 1 did not respond to therapy (6%), and 3 patients did not want to continue with the therapy (19%). Conclusion: Despite the significant improvements in pharmacologic treatment efficacy for HCV reported in published clinical trials, our study suggests that in “real-world” patient care, these medical outcomes may be difficult to achieve. This can primarily be attributed to the fact that a significant number of patients failed to follow up. Also, the overall rate of discontinuation of the therapy owing to adverse events was higher in our study. Nevertheless, it is encouraging that a significant rate of SVR was observed in those who completed the therapy.

Brote epidémico de hepatitis aguda C en pacientes infectados por el virus de la inmunodeficiencia humana

BackgroundRecent studies suggest an increased incidence of acute infection with hepatitisC virus (AHC) in men who have sex with men (MSM) co-infected with HIV. Early treatment with interferon-alpha, alone or in combination with ribavirin, significantly reduces the risk of chronic evolution. MethodsThis retrospective study includes all HIV patients with AHC in our centre from 2003 to March 2013. AHC was defined by seroconversion of HCV antibodies and detection of serum HCV RNA. Results93 episodes of AHC were diagnosed in 89 patients. All but three were MSM with a history of unprotected sex. Thirty-seven (40%) patients had other associated sexually transmitted disease. The 29% (27) had any symptoms suggestive of AHC. HCV genotype 4 was the most common (41%), followed by genotype1. Seventy patients started treatment with interferon-alfa and weight-adjusted ribavirin. Currently 46 have completed treatment and follow-up, reaching 26 of them (56.5%) sustained viral response. ConclusionsThe incidence of AHC in HIV MSM patients from our centre has increased exponentially in recent years; sexual transmission remains the main route of infection. Early treatment with interferon-alpha and ribavirin achieved a moderate response in these patients.

THU0298 Are Anti-La Antibodies A Potential Protection for Hepatitis C Virus Infection in SjÖGren Syndrome? Analysis in 663 Patients

BackgroundA close association between hepatitis C virus (HCV) chronic infection and Sjögren syndrome (SS) was reported 10 years ago. Recently, human La protein has been implicated in facilitating the internal...

Role of interleukin 28-B in the spontaneous and treatment-related clearance of HCV infection in patients with chronic HBV/HCV dual infection

The purpose of this investigation was to evaluate the role of IL28-B polymorphism in the clearance of hepatitis C virus (HCV) in chronic hepatitis B virus (HBV)/HCV coinfection during a long-term follow-up. Thirty-four consecutive patients with HBV surface antigen (HBsAg)-positive/anti-HCV-positive chronic hepatitis were retrospectively enrolled at their first liver biopsy (LB). For all patients, a documented clinical, serological and virological follow-up of at least 3 years (range 3-16 years) after LB and a sample of whole blood for genetic evaluation were available. Of the 24 patients with detectable serum HBV-DNA and HCV-RNA at their first observation, three cleared both HBV-DNA and HCV-RNA, 12 HCV-RNA and five HBV-DNA. Of the seven HBV DNA-positive/HCV RNA-negative patients at enrolment, three cleared HBV-DNA and one remained HBV DNA-positive and became HCV RNA-positive. All three HBV DNA-negative/HCV RNA-positive patients remained unchanged. Compared with the 12 patients with HCV persistence, the 15 patients who cleared HCV were younger, had lower serum alanine aminotransferase (ALT), HCV load, and histological activity index (HAI) and fibrosis score, more frequently had IL28-B CC variant, had been receiving an interferon-based treatment and less frequently cleared serum HBV-DNA. To investigate the relationship between the IL28-B variants and clearance of HCV, excluding the confounding effect of interferon-based treatment, the Mantel-Haenszel test was used, which indicated an association between HCV clearance and IL28-B variants (p = 0.009). In chronic HBV/HCV coinfection, a long-term follow-up showed a frequent spontaneous or treatment-related clearance of active replication of one or both viruses and identified the IL28-B CC genotype as an independent predictor of HCV clearance.

Efficacy of Weeks 4 and 12 Post-therapy HCV RNA Levels in Determining Sustained Virological Response [SVR] after Completing 24 or 48 Weeks of Telaprevir-based Triple Therapy for Chronic HCV Infection

Purpose: The FDA has recently approved an end-point SVR12 for use in HCV trials with direct acting antiviral agents [DAA]. However, 4-6% of patients had viral relapse between 12 and 24 weeks post-treatment with Sofosbuvir despite having achieved SVR12 [EASL 2013]. Our study evaluated whether assessment of serum HCV RNA at 4 and 12 weeks post-treatment was as reliable in predicting SVR as serum HCV RNA at 24 weeks post-treatment in HCV genotype 1 patients who received Telaprevir, PEG-IFN and ribavirin therapy. Methods: A single-center retrospective cohort study was conducted on HCV patients who had achieved end-of treatment [EOT] virological response on therapy with Telaprevir, PEG-IFN and ribavirin therapy between June, 2011 and January, 2013. HCV RNA levels were measured at EOT and post-treatment weeks four, 12 and 24 using a sensitive TMA assay (lower limit of detection of 5 IU/L). Viral relapse was defined as re-appearance of detectable serum HCV RNA between the EOT and post-treatment. SVR was defined as undetectable HCV RNA at 24 weeks post-treatment. Results: One hundred patients were treated from June, 2011 to January, 2013. Thirty-three patients completed 24 weeks of therapy [Group 1], and 25 completed 48 weeks of therapy [Group 2] with undetectable HCV RNA EOT response. In Group 1, at four weeks post-therapy, 23 patients remained negative and one relapsed, with nine remaining non-compliant. In the same group after 12 weeks post-therapy, 21 patients remained negative and two relapsed. And after 24 weeks post-therapy, the remaining 21 patients had undetectable serum HCV RNA. In Group 2 at four weeks post-therapy, 12 patients remained negative and two relapsed with a total of 11 patients being non-compliant. After 12 weeks post therapy, 10 patients remained negative and two relapsed. And after 24 weeks post-therapy, just as those in Group 1, all patients remained HCV RNA undetectable. Conclusion: The study supports that the assessment of serum HCV RNA at 12 weeks post-treatment has a 100% positive predictive value [PPV] in predicting SVR24 in genotype 1 patients receiving DAA therapy. Furthermore, SVR24 is unnecessary, or rather, patients should no longer be required to come back for a third post-therapy visit, which, if implemented, will reduce the cost of disease burden. Unfortunately, however, SVR4 may miss post-treatment early relapses, as it only has a PPV of 89%. Although future prospective or larger retrospective studies would be helpful in further validating these conclusions, according to this data that parallels the FDA's findings, SVR12 is needed while SVR24 is not.

Analysis of hepatitis C virus (HCV) RNA load in platelets of HCV-monoinfected patients receiving antiviral therapy

Introduction. Detection of hepatitis C virus (HCV) has been reported in extrahepatic sites such as peripheral blood mononuclear cells and platelets. Quantitation of HCV-RNA in platelets from patients under antiviral therapy has not been reported.Material and methods. HCV-RNA levels in paired serum and platelet samples of 17 chronically HCV-infected patients were determined at baseline, week 12, end-of-treatment, and 24 weeks after completion of treatment with pegylated interferon plus ribavirin. Quantitation of HCVRNA load was performed using COBAS® TaqMan® HCV Test v 2.0 (lower limit of detection, 25 IU/mL). The cohort predominantly consisted of female (59%) with a mean age of 50.7 ± 10.0 years.Results. Measurements of HCV-RNA in relation to different timepoints of therapy revealed baseline viral load was most frequently detected in higher levels in serum than in platelets (5.6 × 104 lU/mL vs. 379.0 lU/mL; p = 0.0002), a trend also demonstrated in most samples throughout the study. HCV-RNA was also found at low levels (< 25.0-314.0 UI/mL) persistently in platelets of three patients who have lost detectable HCV-RNA in serum during antiviral therapy, resulting in virological relapse.Conclusion. HCV-RNA levels are most frequently detected in higher levels in serum than in platelets, independent of timepoint of antiviral therapy. Further studies with an increase in size of the samples are needed to better evaluate whether or not patients who presented HCV-RNA at low levels in platelets after having lost detectable HCV-RNA in serum during antiviral therapy are at increased risk of relapse of HCV infection during follow-up evaluation.

Frequency and predictors of no treatment in anti-hepatitis C virus-positive patients at tertiary liver centers in Greece

Despite the improving efficacy of antiviral therapy, a significant proportion of chronic hepatitis C patients never start treatment. We determined the magnitude and reasons for no treatment in anti-hepatitis C virus (HCV)-positive patients visiting tertiary liver centers in Greece. We retrospectively enrolled 1146 consecutive anti-HCV-positive patients who visited four physicians at two tertiary liver centers between 2002 and 2010. Treatment was initiated in 628 (55%) of the 1146 patients. In particular, 309 (27%) patients were lost to follow-up before HCV RNA testing. Independent predictors of no HCV RNA testing were first visit before 2007, parenteral drug use, and the treating physician. Of the 837 patients tested for HCV RNA, 768 (92%) were eligible for antiviral therapy, had detectable serum HCV RNA, and no contraindication to treatment. Among them, 140 (18%) patients were lost to follow-up before the initiation of treatment or refused antiviral therapy. Independent predictors of no treatment were the treating physician, absence of liver biopsy or transient elastography (odds ratio: 3.5, 95% confidence interval: 2.3-5.4, P<0.001), and normal compared with elevated alanine transaminase levels (odds ratio: 1.7, 95% confidence interval: 1.1-2.8, P=0.027). A significant proportion (>40%) of anti-HCV-positive patients visiting Greek tertiary liver centers do not receive antiviral therapy. Most of them are lost during the initial evaluation process, whereas the majority (>80%) of eligible patients who complete the initial evaluation eventually start antiviral therapy. The probability of treatment seems to be significantly associated with the treating physician, the alanine transaminase levels, and whether liver biopsy or transient elastography was performed.

A nationwide seroepidemiology of hepatitis C virus infection in South Korea

The aim of this study was to reveal nationwide seroprevalence of HCV infection in South Korea by a large-scale survey. From January to December 2009, a total of 291314 adults underwent health check-up in 29 centres nationwide. The data concerning anti-HCV antibody and biochemical tests were obtained from all participants. Among subjects with positive anti-HCV, such data as HCV RNA, genotypes and treatment detail were additionally analysed. Using an estimated 2009 population of Korea, the age, sex and area-adjusted anti-HCV positive rate was 0.78%. Anti-HCV prevalence in female patients (0.83%) was higher than that in male patients (0.75%). Gradual increase in anti-HCV positivity was observed, from 0.34% in those aged 20-29years to 2.31% in those >70years. The age- and sex-adjusted anti-HCV prevalence varied in different areas, being higher in Busan and Jeonnam (1.53-2.07%), mid-level in Seoul and surrounding districts (0.50-0.61%) and lower in Jeju (0.23%). The comparative analysis of laboratory variables between anti-HCV (+) and anti-HCV (-) group revealed significantly higher levels of alanine aminotransferase and lower levels of serum lipids in anti-HCV (+) group. Among 1 718 anti-HCV positive subjects, serum HCV RNA was measured only in 478 people, of whom 268 (56.1%) patients had detectable HCV RNA in serum. Among 50 patients for whom assessment of response to antiviral therapy was feasible, overall sustained virological response was achieved in 84% of patients. The prevalence of HCV infection is low in South Korea. Studies to analyse risk factors are warranted to reduce HCV infection.

Food Supplement for Therapy of HCV

Hepatitis C is a progressing global health problem. The expense of the exciting regimen for treatment is not available for many patients. Herbal medicines have been used as complementary therapy in the treatment of liver diseases for a long time. Fifty one patients with hepatitis C have been seen in our outpatient clinic, with twelve patients as control. Patients were interviewed to obtain detailed clinical data before and after treatment. The herbal medicines used in the treatment of HCV are Milk Thistle, Phyllanthus, Garlic, Cinnamon, Parsley, Black seed and AKHY-J-25 (mixture of herbs). Every patient received single oral capsule of herbal preparations powder, in early morning on an empty stomach with two cups of water and simple breakfast after two hours, from three months to two years, and twelve patients as control received placebo. The results showed 20% of patients had no detectable HCV RNA in serum at 24 week treatment, 72.6% showed clinical and biochemical improvement with decline of HCV RNA to lower limit and 7.4% showed clinical and biochemical improvement without change in level of HCV RNA.

Coeliac disease and C virus-related chronic hepatitis: a non association

BackgroundA higher prevalence of coeliac disease has recently been reported among patients with HCV-related chronic hepatitis. Moreover, development of clinically overt coeliac disease has been described in a number of HCV-related chronic hepatitis patients during α-interferon therapy. This prospective study was designed to evaluate 1) the prevalence of coeliac disease in patients with HCV-related chronic hepatitis; 2) the prevalence of HCV infection in patients with coeliac disease; 3) whether PEG interferon-α treatment might favour the development of coeliac disease in patients with chronic hepatitis C.Materials and methodsTwo hundred-ten consecutive patients (M/F = 140/70, range of age 35–58 years, median age 46.5 years) with biopsy proven chronic hepatitis C underwent serological screening for antiendomysial and tissue transglutaminase IgA antibodies. One hundred ninety-four coeliac patients (M/F = 52/142, range of age 18–74 years, median age 34 years) were screened for HCV antibodies. Positivity for HCV antibodies in coeliac disease patients was confirmed by detection of serum HCV-RNA by RT-PCR. This work was carried out in accordance to ethical guidelines of Declaration of Helsinki and was approved by Institutional Ethics Committee of the Second University of Naples. All patients gave informed written consent.Results1) none of the 210 HCV-related chronic hepatitis patients were positive for coeliac disease serologic screening; 2) prevalence of HCV infection among coeliac patients was 1.54% (3/194) which is comparable to that reported in the Southern Italy population; 3) PEG interferon-α treatment was not associated with development of coeliac disease either clinical or serological.Conclusions1) coeliac disease is not associated with HCV infection; 2) PEG interferon-α does not trigger celiac disease.

Low Rate of Sustained Virological Response in an Outbreak of Acute Hepatitis C in HIV-Infected Patients

Recent reports have suggested an increased risk of acute hepatitis C (AHC) infection in homosexual HIV-infected men and that early treatment with interferon-alfa, alone or associated with ribavirin, significantly reduces the risk of chronic evolution. A retrospective analysis of 38 HIV-infected patients who were consecutively diagnosed as developing AHC, defined by both seroconversion of anti-hepatitis C virus (HCV) antibodies and detection of serum HCV-RNA in those with previous negative results. Thirty-six patients were men with history of unprotected sexual intercourse with men and two were women with sexual and nosocomial risk factors. AHC infection was asymptomatic in 26 patients; asthenia and jaundice were the most frequent symptoms. HCV genotype 1 was present in 19 patients and genotype 4 in 14 patients. Thirty-five patients received early antiviral treatment with pegylated interferon-alfa associated with ribavirin; 15 of the 32 patients who completed the follow-up (47%) achieved a sustained virological response, as defined by undetectable HCV-RNA 6 months after the end of therapy. There is a risk of sexual transmission of HCV in HIV-infected men who have sex with men. In our experience, early treatment of AHC with pegylated interferon-alfa plus ribavirin in HIV patients achieves poor results.

Lack of short-term increase in serum mediators of fibrogenesis and in non-invasive markers of liver fibrosis in HIV/hepatitis C virus-coinfected patients starting maraviroc-based antiretroviral therapy

The aim of this study was to analyze serum changes in mediators of fibrogenesis and in non-invasive markers of liver fibrosis among HIV/HCV-coinfected patients starting maraviroc (MVC)-based antiretroviral therapy. Patients included in this prospective pilot study met the following criteria: (1) HIV-infection, (2) detectable serum HCV-RNA, and ((3) started MVC. Transforming growth factor-β1 (TGF-beta1), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were measured in serum samples at baseline and 6 months after starting MVC. AST-to-platelet ratio index (APRI) was assessed at the same time points. Twenty-four patients were analyzed. Median (IQR) serum levels at baseline and after 6 months on MVC of TGF-beta1 were 27,295 (20,562-36,844) and 33,753 (18,973-46,130) pg/mL (p=0.116), of MMP-2 were 216 (186-274) and 241 (194-306) ng/mL (p=0.247), and of TIMP-1 were 237 (170-284) and 216 (171-271) ng/mL (p=0.415). APRI levels were 0.99 (0.53-3.46) at baseline and 0.83 (0.48-2.34) at 6 months (p=0.16). Serum mediators of liver fibrogenesis and fibrosis do not change significantly in HIV/HCV-coinfected patients in the short-term after starting MVC. As TGF-beta1 levels have been shown to increase over time in HCV infection and liver fibrosis worsens rapidly in HIV/HCV coinfection, these parameters seem to evolve in a different way in MVC-treated patients.

Long‐term virological follow up of patients with occult hepatitis C virus infection

Patients with occult hepatitis C virus (HCV) infection (HCV-RNA in liver without detectable anti-HCV and serum HCV-RNA) may have viral RNA in peripheral blood mononuclear cells (PBMCs) and in serum after ultracentrifugation, and may present HCV-specific T-cell responses, but it is unknown whether these markers persist to be detectable over time. To perform a prospective virological long-term follow up of patients with occult HCV. Viral markers were tested every 3-4 months during 55.7 ± 20.3 months in 37 patients with occult HCV who were under ursodeoxycholic acid treatment. Viral RNA was detectable in PBMCs of 31 patients during the follow up. In 23 of them, viral RNA in PBMCs was detected intermittently and in the other eight patients HCV-RNA was positive in a single sample. After ultracentrifugation, serum HCV-RNA was detected in 33 patients, being the viraemia intermittently detectable in 28, whereas in the remaining five patients, serum HCV-RNA was positive only once. Only one patient tested always HCV-RNA negative in PBMCs and in ultracentrifuged serum during follow up. Specific Core, NS3, and/or NS4 T-cell responses were found in 31 of the patients. The patient who was always HCV-RNA negative in PBMCs and in ultracentrifuged serum had specific HCV-T-cell responses. Occult HCV infection persists over time with fluctuating viraemia levels that induce and maintain specific T-cell responses against viral proteins.